This invention relates to a vaginal ring containing active medicinal agents, especially estrogens or progestogens along or in combination.
Vaginal rings containing progestationally active steroid hormones or a combination of progestationally and estrogenically effective medicinal agents for preventing conception with or without antiovulatory activity are advantageous whenever formulations of drugs for peroral administration, which contain these active agents, are contraindicated. Vaginal rings furthermore have the advantage of liberating women form a compulsory daily ingestion of tablets. These rings constitute annularly shaped articles which can be introduced into the vagina in a simple manner and which are well tolerated by female patients. As compared to conventional intrauterine pessaries and subdermally administered capsules, these rings have the further advantage that they can be removed and reinserted by the female patient herself at any time.
Vaginal rings made of a synthetic resin, especially silicone elastomers obtained from RTV (room temperature vulcanizing) silicone rubber two-component compositions, e.g. as described in Contraception 8:651 (1973) or from hot-vulcanized silicone rubber products as described in Steroids 21:325 (1973) and which contain active medicinal agents such as steoid hormones, are known per se, e.g. see Fertil. Steril. 21:99 (1970); Amer. J. Obstet. Gynecol. 113:927 (1972); Contraception 8:561 (1973); DOS [German Laid-Open Application] 1,900,196; etc. The active medicinal agent is released from the synthetic resin carrier over a prolonged period of time and is resorbed by the vaginal mucosa.
The steroid hormones contained in the conventional vaginal rings are exclusively those having a progestational effect. Depending on the release rate and amount of progestationally active agent, protection against conception is attained by the use of these rings either with or without attendant antiovulatory activity.
Heretofore known contraceptives in the form of vaginal rings, however, exhibit many known disadvantages. They are produced, inter alia, from RTV silicone rubber two-component compositions, the poor mechanical properties of which are notorious and must first be improved by the addition of fillers. These fillers, however, can disadvantageously influence the release of the medicinally active agent from the vaginal ring. Several conventional vaginal rings are manufactured by vulcanizing suspensions of the medicinal agent in RTV silicone rubber two-component compositions in appropriate molds. The active medicinal agents are released from this type of vaginal ring during the period of application in quantities which are greatly reduced in the course of time as has been reported in Contraception 8:561 (1973).
Considerable differences in the dosage of the active medicinal agents result perforce in qualitative and quantitative differences in the biological and/or contraceptive effect, as well as in the type and extent of undesired side effects during the period of application of the vaginal rings. Known vaginal rings which contain the medicinal agent as a homogeneous suspension in the synthetic resin base have a total weight of about 6.0-15.0 g. If the active medicinal agent is to be released from these vaginal rings in an adequate amount throughout the period of administration, they must contain about 5-30% by weight of the active medicinal agent. This content of effective agent in the drug formulation is uneconomically high as related to the amount of active medicinal agent which is actually released during the period of use. Heretofore, no suitable process has been known for adjusting the level of the desired active drug release rate for a certain active medicinal agent from vaginal rings made of silicone elastomers.
Previously known vaginal rings have been manufactured in part on the basis of synthetic resins which are not entirely physiologically harmless. Thus, RTV silicone rubber two-component compositions containing tin compounds as vulcanization accelerators are utilized for the manufacture of vaginal rings, but such vulcanization accelerators have a toxic effect on the living organism as has been reported in Amer. J. Obstet. Gynecol. 113:927 (1972).
Also known are relatively stiff vaginal rings provided with a metallic spring, similar to a pessary used for the treatment of a prolapse. During their use, erosion of the mucosa can occur in the zone of the posterolateral vaginal vault; see J.A.M.A. 208:949 (1969). British Pat. No. 1,264,732 describes devices consisting of a capsule containing the active medicinal agent on a plastic ring of silicone rubber. However, such devices are poorly suited for mass production due to their construction. Also, these rings lack practicality in their usage becase the inward capsule containing the active medicinal agent hinders the inner ring from lying close to the cervix wall and this implies the risk of its damage, which can be the cause of an increased expulsion rate.
Accordingly, there is still need to solve the problem of providing vaginal rings containing an active medicinal agent which release the active agents over a prolonged period of time, e.g. at least several weeks, regularly and in a uniform quantity required for attaining the desired biological effect, and to overcome the aforedescribed disadvantages inherent in conventional vaginal rings. The present invention fills such needs.